Hemosol Inc.

Lawrence T Wong

Diana H Pliura

Song S Er

Song Swee Er

A chemically modified, crosslinked hemoglobin product suitable for use as a hemoglobin based oxygen carrier comprises a mixture of hemoglobin species and consists essentially of about 40% tetrameric hemoglobin units of molecular weight about 64,000 daltons, up to 5% dimeric hemoglobin units of molecular weight about 32,000 daltons, and the balance oligomeric hemoglobin units of molecular weight up to about 60,000 daltons, the mixed product containing no polymeric hemoglobin species of molecular weight greater than 600,000 daltons. The product can be made directly by a crosslinking reaction under controlled conditions, without the need for separating therefrom high molecular weight species.

Crosslinked hemoglobin product comprising tetrameric and oligomeric

Hemoglobin for forming the basis of blood substitute is modified by crosslinking it by reaction with a polyaldehyde produced by ring opening oxidation of a di/tri-saccharide such as raffinose, wherein the o-saccharide solutions are maintained and the reaction is conducted at a pH from about 5.0-7.0, and at a stoichiometry from about 1:1-4:1 based upon the molar ratio of di/tri-saccharide to hemoglobin tetramers, followed by appropriate reduction of the Schiff base linkages so formed to stabilize them. Careful control of the pH of ring opening of the di/tri-saccharide ensures consistent production of the polyaldehyde without unwanted side products and reaction of this product with the hemoglobin at the specified stoichiometry leads to high yields of stabilized, tetrameric hemoglobin and oligomers thereof of predetermined composition and beneficial properties.

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North York, Canada

Lawrence T Wong